The Cancer Stem Cells Research Program is based on pivotal findings on the origin and nature of cancer stem cells by Program members. The first discovery is that only a small percentage of the cancer cells, the stem cells, drive the growth and metastasis of tumors. These cells must be eliminated if the patient is to be cured. Second, cancers arise because of unregulated self-renewal, the process by which normal and neoplastic stem cells generate new cells at the same developmental stage. As self-renewal is a critical function of both cancer stem cells and their normal counterparts, approaches must be found to characterize and differentiate these self-renewal pathways in order to make cancer stem cells tractable therapeutic targets. The identification of the first cancer stem cells and validation of the cancer stem cell hypothesis both demand and facilitate the integration of basic research and clinical studies. Each cancer stem cell will likely have characteristics unique to the tissue of origin as well as characteristics common to self-renewing stem cells. This Program intends to use the Cancer Center mechanism to facilitate the integration of these important insights into cancer biology with the clinical expertise necessary to translate them to the clinic where they will advance cancer care. To accomplish this we have assembled a large team of leading basic and clinical researchers to work together to address the following Program objectives: 1) To identify the cancer stem cell population in common cancers 2) To investigate potential pathways critical for self-renewal, spread and survival of cancer stem cells 3) To develop new therapies directed against cancer stem cells This Program is comprised of thirty-two members from ten different departments in the School of Medicine with a total of $1.3 million in NCI funding in the last fiscal year. The program members have published 324 reports in the past 5 years. Of these manuscripts, 12% involved intra-programatic and 17% inter-programmatic collaborations, respectively, reflecting the highly productive and collaborative nature of our members. This Program will facilitate further interactions between basic scientists and clinical scientists that will enable us to to exploit the strength of our basic science research to expedite advances in the clinical care of cancer patients.